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Characterisation of a novel protein toxin family secreted by the animal and human pathogen Staphylococcus aureus


Biosciences Institute

Dr T Palmer , Dr T Blower Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Biochemistry Microbiology Molecular Biology Structural Biology

About the Project

Before they can cause disease, bacteria need to colonise their hosts. To do so they must establish a niche among the resident microbiota. Staphylococcus aureus secretes protein toxins using a Type VII secretion system that kill competitor bacteria. The aim of this project is to characterise a novel family of protein toxins that is secreted by the S. aureus Type VII protein secretion system. The project will involve defining the enzymatic activity and cellular targets of the toxins, and identifying neutralising immunity proteins that protect the host strain from self-intoxication. One or more of the toxins will be purified in complex with their immunity protein for structural analysis. A zebra fish embryo colonisation model will be used to examine the role of the secreted protein toxins and their immunity proteins in interbacterial competition.

This project will provide training in a range of complementary techniques, including microbiology, biochemistry, molecular biology, protein expression and purification, and structural biology.

Informal enquiries may be made to

HOW TO APPLY 

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. The Type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria. Nature Microbiology. 10, 16183.
2. A membrane-depolarising toxin substrate of the Staphylococcus aureus Type VII secretion system mediates intra-species competition.” Proceedings of the National Academy of Sciences USA. In press
3. The Type VII secretion system of Staphyloccocus. Annual Reviews in Microbiology. In press
4. EssC is a specificity determinant for Staphylococcus aureus type VII secretion. Microbiology. 164, 816-820.
5. Heterogeneity in ess transcriptional organisation and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains. Molecular Microbiology 93, 928-943.
6. A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems. Science Advances 6, eabb6651.
7. Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences. Biochemical Journal 477, 2401-2419.
8. Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences USA 113, 1706-1713.
9. Viral evasion of a bacterial suicide system by RNA–based molecular mimicry enables infectious altruism. PLoS Genetics 8, e1003023.
10. A processed non-coding RNA regulates an altruistic bacterial antiviral system. Nature Structural and Molecular Biology 18, 185-190.
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